Targeting Head and Neck Cancer by Vaccination

Wang, Chuan; Dickie, James; Sutavani, Ruhcha V.; Pointer, Catherine; Thomas, Gareth J.; Savelyeva, Natalia

doi:10.3389/fimmu.2018.00830

Cited by 44 publications

(42 citation statements)

References 134 publications

(152 reference statements)

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“…Cancer of the head and neck (HNC) is the sixth most common cancer worldwide, with over 500,000 new cases diagnosed annually worldwide 1 . Approximately 80-90% of HNCs are squamous cell carcinomas (SCC).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas

et al. 2020

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Head and neck squamous cell carcinomas (HNSCCs) harbor a subset of cells that are CD44(+) and present with malignancy and radiotherapy resistance. As a key regulator of self-renewal, Nanog expression not only determines cell fate in pluripotent cells but also mediates tumorigenesis in cancer cells; thus, we examined the role of Nanog in CD44 (+) HNSCC. Three HNSCC cell lines, tumor xenografts, and patient tumors were examined. Nanog levels were significantly higher in CD44(+) HNSCC spheroids than in CD44(−) spheroids, and further increased when grown as spheroids to enrich for CSCs. CD44(+) spheroids showed a 3.4-7.5-fold increase in migration and invasion compared with CD44(−) spheroids and were resistant to radiation therapy, which was reversed by inhibiting Nanog. Nanog knockdown also decreased spheroid formation by 66.5-68.8%. Moreover, a phosphokinase array identified upregulated ERK1/2 signaling in CD44(+) HNSCC cells compared with that in CD44(−) cells. ERK1/2 signaling was found to regulate Nanog expression, aiding tumor progression, metastasis, and radiotherapy resistance. In xenograft models, the combination of radiation and Nanog or ERK1/2 inhibition inhibited tumor growth by 75.6% and 79.1%, respectively. In lung metastasis models, CD44(+) cells injected into the tail vein of mice led to significantly more lung metastases and higher Nanog expression level compared with that by ERK1/2-knockdown CD44(+) cells. Finally, in tumor tissues, CD44 and Nanog expression levels were correlated with tumorigenesis in HNSCC patients. Thus, targeting Nanog and the ERK1/2 signaling pathway may prevent or reverse CSC phenotypes and epithelial-mesenchymal transition that drive tumor progression, metastasis, and radiotherapy resistance in HNSCC.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas

et al. 2020

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“…Starting from HPV presence in the tumor cells could also guide the immunotherapy strategies. Starting from the hypothesis that viral antigens are much more immunogenic than those "self", a number of clinical trials have tested vaccination strategies which selectively target the viral antigens, such as E6 and E7 proteins [63]. Results are encouraging but data are still immature.…”

Section: Future Implications On Therapymentioning

confidence: 99%

Management of HPV-Related Squamous Cell Carcinoma of the Head and Neck: Pitfalls and Caveat

Perri

Longo

Caponigro

et al. 2020

Cancers

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Head and neck squamous cell carcinomas (HNSCCs) are a very heterogeneous group of malignancies arising from the upper aerodigestive tract. They show different clinical behaviors depending on their origin site and genetics. Several data support the existence of at least two genetically different types of HNSCC, one virus-related and the other alcohol and/or tobacco and oral trauma-related, which show both clinical and biological opposite features. In fact, human papillomavirus (HPV)-related HNSCCs, which are mainly located in the oropharynx, are characterized by better prognosis and response to therapies when compared to HPV-negative HNSCCs. Interestingly, virus-related HNSCC has shown a better response to conservative (nonsurgical) treatments and immunotherapy, opening questions about the possibility to perform a pretherapy assessment which could totally guide the treatment strategy. In this review, we summarize molecular differences and similarities between HPV-positive and HPV-negative HNSCC, highlighting their impact on clinical behavior and on therapeutic strategies.Cancers 2020, 12, 975 2 of 14 papilloma virus (HPV)-related tumors [1][2][3]. Several lines of evidence support the existence of at least two genetically different types of HNSCC, one virus-related and the other alcohol and/or tobacco and oral trauma-related, characterized by both clinical and biological opposite features [3,4]. Unlike HPV-negative HNSCC, HPV-positive HNSCC often occurs in younger patients with minimal or no tobacco exposure [5,6]. HPV-positive HNSCC, similarly to its HPV-negative counterpart, has a male predominance, with men suffering a three-to-five times higher incidence than women worldwide [7].HPV-positive HNSCC carries a favorable prognosis if compared to HPV-negative tumors. In fact, five-year survival rates for patients with advanced-stage HPV-positive HNSCC are 75-80%, versus values less than 50% in patients with similarly staged HPV-negative tumors [8,9]. The cause of the aforementioned different behavior is the different chemo-and radiosensitivity shown by the HPV-positive and HPV-negative HNSCCs. In fact, several clinical trials have shown that HPV-positive HNSCC patients have a better response to chemotherapy and radiation therapy than HPV-negative cases [10][11][12]. The reasons for this different behavior should be searched in the opposite genetic features which characterize the two types of tumors.In this review, we will analyze the genetics of both HPV-positive and HPV-negative HNSCC, highlighting their impact on the clinical behavior and finally on the therapeutic strategies. Genetics of HPV-Positive HNSCCCarcinogenesis, which is the complex process through which the normal cell is pushed to transform itself into a cancer cell, is very different between HPV-related and non-HPV-related HNSCC. Viral carcinogenesis in HNSCC is partly due to HPV infection, with the oropharynx being the most commonly involved site. HPV-mediated carcinogenesis is driven by a few viral oncoproteins expressed by high-risk HPV genotypes....

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“…79 Finally, tumor-specific TAAs can be generated as a consequence of viral transformation, 80 as in the case of human papillomavirus type 16 (HPV-16)-driven oral and cervical tumors. 81,82 …”

Section: Introductionmentioning

confidence: 99%

Trial watch: Peptide-based vaccines in anticancer therapy

et al. 2018

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Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen

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Targeting Head and Neck Cancer by Vaccination

Cited by 44 publications

References 134 publications

RETRACTED ARTICLE: ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas

RETRACTED ARTICLE: ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas

Management of HPV-Related Squamous Cell Carcinoma of the Head and Neck: Pitfalls and Caveat

Trial watch: Peptide-based vaccines in anticancer therapy

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